Gelatin capsules enclosing a watermiscible vehicle



United States Patent ..2990'334, GELATIN cAPsUnEs EiscLosINc A WATER-1 MISCIBLE VEHICLE Dean Summit, lfLL, assignor to The Upjohn 5 Company, Kalamazoo, M1ch., a corporation of Delawere I No Drawing. Filed June 29, 1959, Ser. N0.823,291

. 3 Claims. (Cl. 167-83) drogen, methyl and ethyl; R

2,990,334 Patented June 19 61 7 -The present invention provides a sealed gelatin-capoxolane compound having the formula I I r I sule enclosing a vehicle containing a water-miscible di H-G-o R wherein R is a member of the class consisting of hyis a member'of the class consisting of hydrogen, methyl .and ethyl; and'iReflis a member of the class consisting of Ihydrog'en,*methyl, carbinol and ethylol. The vehicleis inert'togelatin, is water-miscible, and possesses superior solubilizing and dispersing action on a Wide variety of components. Since Hard-gelatin capsules are usually composed of two parts,

a cap and a body which are fitted together after the body hasbeen filled with an appropriate component or components. They are also made in a wide variety of sizes. Both soft capsules and hard capsules can enclose a wide variety of components.

The inherent mutual afiinity of water and gelatin has resulted in serious difiiculties in the art of encapsulating components into either soft or hard capsules. Special precautions are required to keep the water content in said components and in any accompanying vehicle at the Otherwise the water exerts deleterious efiects on the gelatin. In the case of soft capsules, water-im---f---- miscible oils are widely used as vehicles for thexcom-f ponents to be encapsulated. In the case of hard capsules, the materials to be encapsulated must be dried tov aminimum content of water prior to encapsulation. If special precautions to exclude water from the vehicle and the components are not followed carefully, both hard and soft capsules will break down during the encapsulation process; l fthe capsules do survive this process, "storage after manufacture results insoftening of the capsules, the appearance of small holes 'atthe point of any contact between water and the gelatin shell of the capsule, the gradual loss of the acceptable elegant character of the" capsules and The aforesaid difiiculties in the manufacture, storage,

even loss of the encapsulated components.

product elegance and use of soft and hard. capsules have;

caused a long-felt need for a vehicle which is watermiscible, inert togelatin and has a superior solubilizin and dispersing action on a wide variety of components to be encapsulated. A particularly acute difiiculty arises'in' the use of soft capsules enclosing water-soluble components. Since oily vehicles are customarily used tocarry' the components, ready dispersion and solution of the said components does not'occur in aqueous media due to retarding of dispersion-by the oil. For example, after the oral ingestion of; gelatincapsules for therapeutic purposes, the encapsulated'components must normally be,- come dissolved in the aqueous mediumin the gastro-; 6 intestinal tract before absorption can take place. The" components in oily vehicles must be leached away from the oil bythe aqueous medium before the absorption can occur. Moreover, the use of oily vehicles in which many of the components to be encapsulated are insoluble greatly: hampers the practical manufacture of filled gelatin cap.- sules. Many components must be encapsulated in larger capsules than would be necessary if a water-miscible vehicle with no adverse .efiects on gelatin were available. It has been found also that some oily vehicles, particularly those carrying suspendal components, are verydiflicult to ca s-mate because 'of'higli' viscosity.

-methyl or ethyl; and R the vehicle inhibits the action of water and hygroscopic substances 'on gelatin, both 'water and hygroscopic-substances, in addition to other components, canv be carried in the vehicle. I s r 1: 1 :1 The present invention obviates the use of oily vehicles as carriers for components to be encapsulated. Moreover, the capsule. of the present invention provides ready dispersion of the' encapsulated components upon contact of thecapsule with an aqueousmedium.

The'inventive capsule encloses avlehicle containing a compound ofthe formula g H is hy en; is hydrogen, methyl, carbinol or ethylol.- Thepreferred compound is 2,2-dimethyl-4-carbinol-l,3-dioxolane. The other dioxolane compounds of this class, suitable in the vehicle, are

wherein R s y r en. meth jo hyl;

1,3 -dio2 rolane, 4 m'ethyl-1,3-dioxolane,

4-carbinol-l,3'-dioxolane,

4-ethylol-l,3-dioxolane, 2,2-dimethyl-l,3-dioxolane, 2,2, 4-trimethyl-L3-dioxolane, Y 2,2-dim'ethyl-4-e1:hylol-1,3-diox0lane, 2,2-diethyl-l,3-dioxolane, 2,2 diethyl-4-methyl-1,3-dioxolane, 2,2-diethyl-4-carbinol-1,3-dioxolane, 2,2-diethyl-4-ethylol 1,3 dioxolane, 2-methyl-1,3-dioxolane,

2,4-dimethyl-l,3.-dioxola.ne,

2-methyl-4-carbinol-1,3-dioxolane, 2-methyl-4-ethylol-L3-dioxolane, 2'-ethyl-l,3-dioxolane, 2-ethyl-4-methyl-1,3-dioxolane,

- 2-ethyl-4-carbinol l,3-dioxolane,

2-etliyl 4-ethylo1-1,B-dioxolane, 2-ethyl-2-methyll-1,3-dioxolane, 2,4- dimethyl2-ethyl-l,3-dioxolane, 2-ethyl-2-methyl-4-carbinol-l,3-dioxo1ane, and

2-ethyl-2-methyl-4-ethylol-l,3-dioxolane.

0 capsule is protected from solution in,

The said vehicle is ther, it inhibits the action of or substantial amounts of water on gelatin capsules. v[Ihe in the gelatin, in the diluted hicle much greater than the water, so that they capsule retains practically inert to gelatin. Furhygroscopic components-- i tenianutactur ns- Mo e. water-miscible nature.

of the vehicle furthers ready dispersion and solution in water of the encapsulated components. 'IEhe-eQrnponents-are dissolved, suspended or emulsified inihpwt hicleby conventional means prior to encapsulation into the gelatin. capsules. 1 Encapsulation into the gelatin shells is carried out by means and methods known in the art. In the case of hard capsules, the known techniques for sealing the fitted bod'yand cap can be utilized.

The dispersing and solubilizihg properties of the vehicle of the invention. are such'that the vehicle can be used for the encapsulation of bothliquid and solid comasaqsse ponents. The vehicle will dissolve both water-soluble and waterin'soluble components. For example, flavors; perfumes,' essences, foaming agents, surfactants, cosmetics, food products, .witamins and medicinals can be ehpapsulated t byutilizing said vehicle.

Hard gelatin capsules and soft gelatin capsules. were exposed-to the action ofsa vehicle containing 2,2-dimethyl-4.-lcarbinol-1,3-dioxolane to ascertain the effect on the gelatin of vaiious concentrations of water present in the vehicle'a.-The condition of the capsules was observed at various tiineszand the observations recorded in Table I. The observations were made at 25 degrees centi'grade.

p V TABLET 25 C. I 2,2 dimethyl4-carbinal-I3 dioxolane ..EXAMPLB. 3

Soft gelatin capsules enclosing a vehicle containing novobiocin are prepared as follows:

A solution of the novobiocinin the water andfiioxolane ts-Prepared and encapsulatedby the usual techniques into 2.65 minim soft capsules. The finished capsules do not soften or leak. Each capsule provides approximately 1000 mg. of the medicament. The capsules are used orally in the treatment of staphylococcie infections. EXAMPLE 4 containing Soft gelatin capsules enclosing a vehicle an antiperspirant are prepared as follows: Aluminum chlorhydroxide complex gms.... Purified water, U.S.P.. mls 100 2,2-dimethyl-4-ethylol-1,3-dioxolane, q.s; ad mls 1000 aluminum chlorhydroxide is dissolved in the wa- The solution is made up to volume with the dioxostability of gelatin capsules in vehicle containing 1 Percent of Water in the Vehicle 7 p 1o 20 so Hard Capsules Stable- Stable- Softened- Sottezied- Bottened-. p BSdays. v-,-38 days. ehours. 1%,hrs. lhour. SottGapsules do do swelled Swelled-' Dissolved tifidays. 201mm tshours.

These data indicate that as much as ten percent water does not adversely alfect either soft or hard gelatinzcapsules in the presence of the 2,2-dimethyl 4- .carbinol-.L5 dioxolane. Y

The following examples set forth the. best mode con.- templated by the inventor of carrying out'hisinvention but are not to be construed as limiting the invention. p

Soft gelatin capsules encl'osing a vehicle containing aqueous lemon juice concentrate are prepared as follows: Aqueous lemon juice concentrate mls e 50'. 4-carbinol-1,3-dioxolane ..mls 950 The two ingredients are welljmixed and encapsulated by the usual techniques into'soft capsules provided with.

a tip. The finished capsules do not'softe'n or leakpjAt.

the time of use the tip is severed'or punctured to fa'cilitate expression of the capsule contents for flavoring.

EXAMPLE 2 Soft gelatin capsulesenclosinga vehicle containingcholine chloride are prepared as follows:

Choline chloride gm s00 Pnrified water, U.S.P ...mls 40 2;,ethyl12 methyl-1,3-dioxolane, q.s. ad mls 1000 'The cholinechloride 'is mixed with the water andthe mixture stirred into thedioxolane. The whole is encapsulated the usual'tech'niques into 6.75 minim. soft capsules.- Eaehcapsjule'encloses approximately 200 mg. of the choline c hlo'ride. The finished capsules do notv softener-leak; v The capsules are used in. liver disorders sueh iis fiitty degeneration.

lane. and encapsulated 'by the 'usual techniques into I 16 soft capsules provided with a'tip. Thefinished capsules do not soften orleak. At the time of use the tip is severed or puncturedto facilitate expression of the; capsul'ebontent's. V t Y EXAMPLE '5 -*Sealed hard gelatin capsules enclosing a vehicle containing; a vitamin'mixture are prepared as'follows:

T-hewell mixed ingredients are encapsulated by the usual techniques into hard-capsules. The sealed-finished capsules'do not soften or leak. They are used in the oral treatment of vitamin deficiencies.

EXAMPLE 6 Soft gelatin capsules-enclosing avehicle containing roseswater' are. prepared Zas ,followsz.

Rose water ink The ingredients are well mixed and encapsulated by the usual techniques into soft capsules. The finished capsules do not soften or leak. At the time of use, the capsules are placed in water wherein rupture of the gelatin shell and dispersion of the capsule contents occur readily.

EXAMPLE 7 Sealed hard gelatin capsules enclosing a vehicle containing a detergent are prepared as follows:

Sodium lauryl sulfate gms 5 Purified water, U.S.P. mls 7 2,2-dimethyl-4-carbinol-1,3-

dioxolane, q.s. ad mls 100 A solution of the sodium lauryl sulfate in the water is prepared and made up to volume with the dioxolane. The Whole is encapsulated by the usual techniques into hard gelatin capsules which are then sealed. The finished capsules do not soften or leak. At the time of use the capsules are placed in water wherein rupture of the gelatin shell and dispersion of the capsule contents occur readily.

It is to be understood that the invention is not to be limited to the exact details of operation or exact compositions shown and described herein as obvious modifications and equivalents will be apparent to one skilled in the art, and the invention is therefore to be limited only by the scope of the appended claims.

What is claimed is:

1. A sealed gelatin capsule enclosing a liquid watermiscible vehicle containing (1) a water-miscible dioxolane compound having the formula wherein R is a member of the class consisting of hydrogen, methyl and ethyl; R is a member of the class consisting of hydrogen, methyl and ethyl; and R is a member of the class consisting of hydrogen, methyl, carbinol and ethylol and (2) from 0 to about 10% of water based on the volume of said vehicle.

2. The capsule of claim 1 wherein the vehicle contains in addition a medicinal component.

3. The capsule of claim 1 wherein the vehicle contains in addition a vitamin component.

References Cited in the file of this patent UNITED STATES PATENTS 2,667,268 Griffin Jan. 26, 1954 2,872,377 Beiler Feb. 3, 1959 FOREIGN PATENTS 553,398 Canada Feb. 18, 1958 OTHER REFERENCES Amer. Perfumer and Aromatics, February 1956, p. 25. 

1. A SEALED GELATIN CAPSULE ENCLOSING A LIQUID WATERMISCIBLE VEHICLE CONTAINING (1) A WATER-MISCIBLE DIOXOLANE COMPOUND HAVING THE FORMULA 